A nonrandom association between gastrointestinal stromal tumors and myeloid leukemia.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are KIT-positive mesenchymal tumors of the gastrointestinal tract that are driven by activated KIT-signalling or platelet-derived growth factor receptor-alpha (PDFGRA) signaling. These tumors most commonly occur in the stomach and small intestine and encompass a clinical spectrum from benign to malignant. In the current study, the authors examined long-term follow-up data of 1892 GIST patients from the U.S.
BACKGROUND: Nine patients (2 with gastric GISTs and 7 with GISTs of the small intestine) developed myeloid leukemia. There were 6 patients (4 women and 2 men) with acute myeloid leukemia (AML), including 1 case of promyelocytic and 1 case of myelomonocytic leukemia, and 3 patients (2 men and 1 woman) with chronic myeloid leukemia (CML).
RESULTS: The leukemias developed 1.7 to 21 years after the GIST (median interval, 6 years). None of the GIST patients had received radiotherapy or chemotherapy prior to the leukemia diagnosis. Eight of 9 patients died of leukemia, and none died of GIST. All but 1 GIST case was found to have a low mitotic rate (0-1 per 50 high-power fields); however, tumor size varied from 3 to 18 cm (median, 4.5 cm). Standardized incidence ratios (SIRs) and their 95% confidence intervals (95% CIs) were calculated comparing the incidences of AML/CMLs in GIST patients with those in the 2000 through 2003 U.S. population. In GIST patients, the risk of AML was found to be significantly higher for women (SIR of 5.14; 95% CI, 1.34-11.4) and overall (SIR of 2.96; 95% CI, 1.07-5.8). There was a slightly increased risk for CML, but this was not statistically significant (SIR of 3.71; 95% CI, 0.7-9.1).
CONCLUSIONS: Additional epidemiologic, clinical, and pathogenetic studies are needed to understand the apparent nonrandom association between GIST and myeloid leukemia.